| Objective: To observe the effect of surgical trauma on the behavior of aged rats to learn, and to further explore dexmedetomidine(dexmedetomidine,Dex) for postoperative cognitive dysfunction(postoperation cognitive dysfunction,POCD) model of the hippocampal formation of aged rats(CA1 region, CA2 region, CA3 region and dentate gyrus(DG)) c-fos and neuronal nitric oxide synthase(n NOS) expression.Method: 1. The use of laparotomy splenectomy method of making POCD rat model. 114 trained healthy male SD rats aged 18 months old, with a random number table, was divided into the three set points according to the time order of 1,3,7 days after the surgery. Each large group was divided into five groups: normal control group(n = 6), normal saline(NS 2ml / kg n = 8), the surgery group(saline 2ml / kg n = 8), low dose Dex group(Dex 3μg / kg n = 8), high dose Dex group(Dex 12μg / kg n = 8). Except the normal control group, the remaining four groups of rats were treated with 1% sodium pentobarbital(30 mg / kg, ip) anesthesia, and are to be turned back reflex, according to the set of tail vein injection drug dose, the capacity of 2ml / kg, pushed within 10 minutes. 10 minutes after the administration, except normal saline, the other three groups of rats intraperitoneal surgery(laparotomy + splenectomy). 2. 1,3,7-day learning and memory with the Morris water maze test in rats after anesthesia or surgery. 3. The brain of rats in each group, sagittal split into two halves, the left half of the brain was observed paraffin c-fos and n NOS expression by immunohistochemistry in hippocampal formation. We counted the same in different regions of hippocampal coronal high power(400 times) vision positive cells per unit area of positive cells, and measured the mean gray values, which were statistically analyzed. 4. The right half of the brain hippocampal tissue structure by immunoblotting(Western blot). We observed the expression of hippocampal structure of c-fos and n NOS protein.Results: 1.MWM Results: Compared with normal control group, 1,3,7 days after the surgery, the saline group was no difference in escape latency time and the number of crossing the assumed platform. The escape latency time of the surgery group was significantly prolonged(P <0.01), crossing the assumed platform number reduction(P <0.01 or P <0.05); compared with the surgery group, Dex low-dose group1,3 days after the surgery and high dose group 1,3,7 days after the surgery, of which Dex escape latency was significantly shorter(P <0.01), and the number of crossing the assumed platform was increased(P <0.01 or P <0.05). 2. Immunohistochemical results: ①c-fos expression: ⑴ One day after the surgery, the normal control group hippocampal formation districts had a certain amount of c-fos expression. Compared with the normal control group, there was no significant difference in the saline group hippocampal formation districts of c-fos(P>0.05). The surgical group hippocampal formation districts c-fos expression was increased(P <0.05). Compared with the surgical group, Dex low dose group and high dose group hippocampal formation districts c-fos expression was decreased(P <0.05). ⑵ Three days after the surgery, compared with the normal control group, the expression of the saline group hippocampal formation districts of c-fos was no significant difference(P>0.05). The expression of the surgical group hippocampal CA1, CA3 and DG region area of c-fos was increased(P <0.05). Compared with the surgical group, Dex low dose group and high dose group hippocampal CA1, CA3 region and the expression of c-fos DG area were reduced(P <0.05). ⑶ Seven days after the surgery, there were no statistically significant difference in the expression of Dex low dose group, high dose group, normal control group, saline group, surgery group hippocampal formation districts of c-fos(P>0.05). ②n NOS of expression: ⑴ 1,3days after the surgery, the hippocampal formation of the district had a certain amount of n NOS expression. Compared with the normal control group, there was no significant difference in the expression of n NOS districts saline hippocampal formation(P>0.05). The surgical group hippocampal CA1 region, n NOS expression in CA3 and DG region area was increased(P <0.05). Compared with the surgical group, Dex low dose group and high dose group hippocampal CA1, n NOS expression in CA3 and DG regions had reduction(P <0.05). ⑵ Seven days after the surgery, compared with the control group, the saline group had no significant difference in the n NOS expression in the hippocampal formation districts(P>0.05), The n Nos expression of the surgical group hippocampal DG region was increased(P <0.05); Compared with the surgical group, Dex high doses n NOS expression in hippocampal DG area had reduction(P <0.05). 3. Western blot results: ①1,3 days after the surgery: Compared with the normal control group, no significant difference in the saline group hippocampal formation c-fos and n NOS protein expression in hippocampal structure(P>0.05). The surgery group c-fos and n NOS protein expression was increased(P <0.05). c-fos protein expression and n NOS of Dex low dose group and high dose group compared with the hippocampal formation surgery group had reduction(P <0.05). ② Seven days after the surgery: No statistical significant difference in the hippocampal formation of c-fos and n NOS protein expression of the normal control group, the saline group, the surgery group, Dex low dose and high dose group(P>0.05).Conclusion: 1. MWM test results show Surgical trauma can cause old rats to have POCD, and significantly increase the expression of c-fos and the hippocampal formation of n NOS. The expression of c-fos and n NOS prompt enhancement may be related to the pathogenesis of POCD. 2. Preintravenous Dex can significantly cut down the protein expression of the elderly rats hippocampal formation c-fos and n NOS, with 1, 3 days after the surgery, and improve elderly POCD model rats’ spatial learning and memory, which may have a preventive and mitigating Dex surgical trauma-induced morphological basis POCD. |
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